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Effects of a low FODMAP diet on the symptom

management of patients with irritable bowel
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Cite this: Food Funct., 2024, 15, 5195

syndrome: a systematic umbrella review with the
meta-analysis of clinical trials†
Masoumeh Khalighi Sikaroudi,a,b Sepideh Soltani,c Seyed Mojtaba Ghoreishy,e
Zohreh Ebrahimi,e Farzad Shidfar *d,e and Afsaneh Dehnadf

A low FODMAP diet (LFD) is a common restrictive diet to manage the symptoms of irritable bowel syn-
drome (IBS). However, there is no consensus on the alleviating effects of this diet. Herein, a systematic
umbrella review with meta-analysis was conducted to investigate the effect of an LFD on IBS symptoms
and its secondary outcomes in patients, which were not reported in previous meta-analyses. We per-
formed a systematic literature search in PubMed, Scopus, and ISI Web of Science up to December 2023.
The methodological quality of systematic reviews and their included trials was evaluated using AMSTAR 2
and the Cochrane risk of bias, respectively. The certainty of the evidence tool was evaluated using the
GRADE approach. The data related to IBS symptoms, quality of life (QoL), microbiome diversity, and stool
short-chain fatty acids were extracted. A random-effect (if RCTs ≥ 6) or fixed-effect model (if RCTs < 5)
was used to recalculate effect sizes and 95% CIs and report them in both qualitative and quantitative
terms ( pooled risk ratio, Hedges’ g, and weighted mean difference). A total of 658 articles were initially
identified, with 11 meta-analyses and 24 RCTs reporting 28 outcomes with 1646 participants included. An
LFD significantly affected the clinical improvement of total symptoms according to the IBS-SSS question-
naire (RR: 1.42; 95% CI: 1.02, 1.97; P = 0.04) in all the subtypes of IBS and also had favorable effects on
stool consistency (WMD: −0.48; 95% CI: −0.902, −0.07) and frequency (WMD: −0.36; 95% CI: −0.61,
−0.10) and some other GI symptoms in both less and more than 4 weeks of diet intervention except for
stool consistency, which needed more than 4 weeks of LFD implementation. A significant QoL improve-
Received 2nd September 2023, ment was observed but not in the anxiety and depression state. Furthermore, some studies showed that
Accepted 8th March 2024
an LFD may increase fecal pH and dysbiosis and reduce SCFA and the abundance of Bifidobacterium. In
DOI: 10.1039/d3fo03717g conclusion, an LFD can alleviate symptoms and QoL in IBS patients, although dysbiosis may occur.
rsc.li/food-function Considering the low certainty of evidence, strong RCTs with more appropriate designs are needed.

1. Introduction
Irritable bowel syndrome (IBS) is a disorder of gut–brain inter-
action with an outbreak of 4–5% 1,2 and is characterized by
a
Department of Clinical Nutrition, School of Nutritional Sciences and Dietetics, changes in bowel habits (constipation and diarrhea) and
Tehran University of Medical Sciences, Tehran, Iran chronic abdominal pain.3 The pathophysiology of IBS is not
b
Colorectal Research Center, Iran University of Medical Sciences, Tehran, Iran fully understood but alterations in visceral nerve susceptibility,
c
Yazd Cardiovascular Research Center, Non-communicable Diseases Research
bowel permeability, psychological agents, the gut–brain axis,
Institute, Shahid Sadoughi University of Medical Sciences, Yazd, Iran
d
Nutritional Sciences Research Center, Iran University of Medical Sciences, Tehran,
and the gut microbiota and unfavorable responses to foods
1449614535, Iran. E-mail: [email protected]; Fax: +98-21-88622533; have been reported as susceptible factors.4–8
Tel: +98-21-88622755 Symptoms such as recurrent abdominal pain, changes in
e
Department of Nutrition, School of Public Health, Iran University of Medical stool consistency and frequency, flatulence, and bloating can
Sciences, Tehran, 1449614535, Iran
f
considerably affect the quality of life of patients.9 Patients with
Department of English Language, School of Health Management and Information
Sciences, Iran University of Medical Sciences, Tehran, Iran
IBS present manifold symptoms, but medical treatment is
† Electronic supplementary information (ESI) available. See DOI: https://doi.org/ commonly effective in alleviating only one or two principal
10.1039/d3fo03717g symptoms. In addition, drugs alone are not effective in all

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Review Food & Function

cases.10,11 In this situation, dietary management is considered 2.1. Literature search

a treatment option.12 Both authors (S. S. and M. K. S.) performed an independent
The majority of IBS patients report the onset or exacerbation systematic literature search based on the Preferred Reporting
of symptoms with some foods.13,14 The connection between food Items for Systematic Reviews and meta-analyses: the PRISMA
and gastrointestinal symptoms is evident in IBS, and presently, a statement.28 The systematic search was carried out in PubMed/
large number of patients conform to an elimination diet plan, Medline, ISI Web of Science, and Scopus databases up to
where special food components are removed from their December 2023 for related systematic reviews and meta-ana-
regimen.12 Traditional dietary advice including regular meals lyses of randomized controlled trials (RCTs) evaluating the
with reduction of fiber intake and lactose-containing foods is not effect of an LFD on different outcomes of patients with IBS.
sufficient in relieving symptoms for IBS patients.3 One of the We used the following search terms: “FODMAP” OR “fermenta-
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elimination diets that was recently devised is a low FODMAP diet ble oligosaccharides, disaccharides, monosaccharides and
(LFD), restricting fermentable oligosaccharides, disaccharides, polyols” AND “irritable bowel syndrome” OR “IBS” OR “func-
monosaccharides, and polyols (FODMAPs).2,11 These short-chain tional gastrointestinal” AND “systematic review” OR “meta-
carbohydrates are present in diverse fruits, vegetables, legumes, analysis”. The complete information of the search strategy is
dairy products, artificial sweeteners, and foods containing shown in Table S1.† Additionally, we screened eligible studies
wheat.3 These are incompletely absorbed in the small intestine in the reference lists of relevant publications.
and can lead to gas generation, diarrhea, cramping, and flatu-
lence via gut microbial fermentation mostly in the colon, and 2.2. Study selection
incremented water maintenance via osmosis in both the colon
and the small intestine.15 The titles and abstracts of the eligible systematic reviews and
Several studies have approved that the gut microbiota, gut meta-analyses were screened by the same authors who per-
barrier, and visceral sensation are influenced by dietary habits formed the search. After removing the duplicates, the eligible
and FODMAPs.16,17 Recently, gut microbiota-targeted treat- studies were selected for inclusion in the umbrella review
ment18 and dietary approaches11 have been extensively used in according to the following criteria: (1) meta-analyses of RCTs
clinical practice for the treatment of IBS.19 According to recent were performed in adults aged 18 years or older, (2) reporting
research, following the restriction phase, treatment with effects of low FODMAP diet (defined as a limit FODMAPs of
Rifaximin and probiotics and diet personalization phase are 0.5 g per meal10) on different outcomes, (3) having a control
recommended.20 group for comparison, given that the diet intervention could
The results of recent meta-analyses showed that an LFD is consist of a habitual diet, high FODMAP diet, sham diet, tra-
associated with improving the symptoms of IBS.21–23 However, ditional dietary advice, and standard dietary advice based on
this association has not been conclusively confirmed and NICE guidelines, (4) addressing patients with any type of IBS
there are some doubts in this regard. Therefore, for the first ( predominant constipation, predominant diarrhea, and mixed
time, we designed a systematic umbrella review with meta-ana- bowel habits), and (5) primary RCTs having a dietary interven-
lysis to investigate whether prescribing an LFD can reduce the tion of at least 2 weeks. Studies checking the effect of other
primary and secondary clinical symptoms of patients with IBS diets on the symptoms of patients with IBS, such as gluten
and the complications of this diet. free, elimination diet or restricted just one item of FODMAPs
Umbrella review studies are being used to offer a wide per- were excluded. Also, studies were excluded if they were confer-
ception of published meta-analyses on a special subject. ence abstracts, non-comparative trials, studies with insuffi-
Evaluating the quality of the published meta-analyses and the cient data to enable calculating effect sizes, and studies based
precision of the estimations gained by research may help offer on secondary sources and reporting the same data in more
more reliable evidence for the connection between dietary than one publication. Any disagreements were resolved by con-
components and the risk of disease.24 sensus discussion between investigators.

2.3. Data extraction

2. Materials and methods The following information was extracted from full texts of qua-
lified meta-analyses by both researchers (S. S. and M. K. S.)
This umbrella review summarizes previously published sys- independently: first author, year of publication, number of
tematic reviews and meta-analyses. This study was conducted contributors (intervention and control), number of RCTs con-
according to the “Cochrane Handbook for Systematic tained in the primary meta-analysis, number of primary RCTs
Reviews”25 and the “Grading of Recommendations Assessment found from the same meta-analyses conducted in a similar
Development, and Evaluation” (GRADE) handbook.26 The population, effect size on each outcome and type of tool for
framework of study was designed according to “The Preferred assessment (GI symptoms assessed with IBS-SSS or visual
Reporting Items for Overviews of Reviews” (PRIOR) state- analog scale (VAS) or Birmingham IBS symptom score (BISS) or
ment.27 The protocol of this study was registered at the gastrointestinal symptom rating scale (GSRS) questionnaire:
PROSPERO database of systematic reviews (ID number: total symptoms, clinical improvement in IBS-SSS, abdominal
CRD42023388368). pain intensity, abdominal pain frequency, abdominal disten-

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tion, dissatisfaction of bowel habit, interference on life in secondary outcomes of IBS from preliminary clinical trials that
general, bloating, flatulence, urgency of defecation, borboryg- were not reported in previous meta-analyses. The effect sizes
mus, belching, incomplete defecation, heartburn, nausea; and 95% CIs in all the meta-analyses were recalculated using a
stool habits evaluated by Bristol stool form (BSF) or VAS or random-effect model if the number of studies was more than
GSRS: stool consistency, stool frequency, diarrhea, consti- six trials; otherwise, the fixed-effect model was used when the
pation; IBS-QoL questionnaire for quality of life; anxiety and number of studies was less than five.34 Also, for the outcomes
depression with HADs questionnaire), and type of diet inter- whose effect sizes were not reported in the meta-analysis, we
vention in the control group (mentioned above). A systematic extracted data from the primary trials, and the effect size was
review was conducted on the effect of an LFD on microbiome calculated based on the original data. In the case of outcomes
diversity, breath test, and alternation in stool short chain fatty with identical units and using the same tool assessment for
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acids (SCFA). In addition to data extraction from meta-ana- gathering data (for example symptoms questionnaire), pooled
lyses, the following data extracted from each primary trial con- estimates were stated as weighted mean differences (WMDs)
tained in the qualified meta-analyses and systematic reviews with 95% CIs, whereas under other circumstances, when
were obtained: the first author’s name, publication year, sex, different tools were used to evaluate an outcome, we used
age, contributor number, study design, duration of interven- Hedges’ g technique and 95% CI. If more than 90% of the
tion (weeks), type of IBS, IBS diagnostic method (manning, studies used the same instrument for outcome assessment, we
NICE criteria, and ROME I–IV), amount of FODMAPs, data of also performed a sensitivity analysis. Relative risk (RR) and
outcomes at baseline and after intervention in each group. 95% CIs were considered for dichotomous outcomes with raw
data (number). Recalculation of the effect size was applied to
2.4. Assessment of the confidence and quality of evidence address both within- and between-study heterogeneity.35 The
Both authors (S. S. and M. K. S.) independently performed quality results of each eligible meta-analysis presented in the forest
evaluations. Any discrepancies were resolved through consensus plot were used for the overall analysis. Publication bias was
discussions. To assess the methodological quality of the pub- assessed by Egger’s tests if there were ten or more trials (sig-
lished meta-analyses, we employed “A Measurement Tool to nificance level of P < 0.10).36 Trim and fill corrective tests were
Assess systematic Reviews version 2.0” (AMSTAR 2).29 This scale used for outcomes with significant publication bias and had
ranged from 0 to 11, based on which meta-analyses with scores of asymmetry between studies to adjust our analysis for the
≥8 were ranked high quality, meta-analyses with scores of 4–7 as effects of publication bias on the available data.37 In all the
medium, and scores of ≤3 as low quality. Similarly, the quality of analyses, heterogeneity was evaluated with the I2 statistic and
the prime RCTs included in each meta-analysis was assessed by Cochran’s Q test, and I2 > 50% and P-heterogeneity < 0.1 were
two separate reviewers using the Cochrane collaboration’s instru- considered as fundamental heterogeneity.25
ment to determine risk of bias in randomized trials.30 If there were six trials for each outcome, a subgroup ana-
lysis was performed. Subgroups were created according to the
2.5. Grading of the evidence study design, study quality (high, moderate, and low), duration
The certainty of evidence was evaluated using the GRADE of intervention (week), control group regimen, co-intervention
method.26 This method ranks the certainty of evidence as high, with diet modification, assessment tools for each outcome,
medium, low, or very low. Randomized controlled trials were type of IBS, and diagnosis tool. Subgroup and publication bias
initially rated as high certainty evidence, and then downgraded analyses were performed using the STATA software, version
according to predefined criteria. The criteria utilized to down- 17.0 with statistical significance defined as P < 0.05.
grade evidence included study limitations (weight of studies indi-
cating the risk of bias as evaluated by the Cochrane risk of bias
instrument),31 incompatibility (the between-study heterogeneity 3. Result
that was not considerably explained; I2 ≥ 50% and
P-heterogeneity < 0.10),32 indirectness (factors related to popu- After reviewing the titles and abstracts, a total of 658 articles was
lation, intervention, or comparison factors that confined the gen- retrieved by searching the aforementioned databases, and 312
eralizability of the results),33 imprecision (for continuous results: duplicate records and 249 irrelevant studies were removed.
optimal data size did not estimate and/or the 95% CIs for the Consequently, 101 full texts were reviewed in detail for eligibility.
WMDs are broad or the point estimate did not surpass the mini- Finally, 19 meta-analyses8,21,38–50 and 19 systematic reviews con-
mally important difference; for two part results: optimal data size tributed by 49 RCTs were assessed, among which 11 meta-
did not estimate and/or the 95% CI contain the zero amount and analyses8,21,38–45,50 and 24 RCTs3,51–73 with 1646 participants were
the lower and/or upper borders of the 95% CI were <0.9 and considered eligible for the analysis of the effect of an LFD on
>1.1),32 and evidence of publication bias (the outcomes of more different outcomes of IBS patients. The literature search process
than 10 studies were evaluated).31 and reasons for exclusion are shown in Fig. 1 and Tables S2, S3.†

2.6. Data synthesis and statistical analysis 3.1. Study characteristics

The umbrella review and analysis were performed for data of The findings of the published meta-analyses were classified
meta-analysis studies. Moreover, we meta-analyzed the data of into 27 outcomes, among which 22 had sufficient data for ana-

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Fig. 1 Literature search and study selection process.

lysis. The RCTs from the systematic review and meta-analysis used IBS-QoL tool3,54,56,57,60,63,65,67,72,73), and anxiety and
evaluated the effect of different diets (low in FODMAPs (range: depression (n = 5 studies used HADs3,54,65–67). Primary trials
1.89 to 39.18 g) versus other diets with different amounts of were published between 2012 and 2021. All the studies
FODMAPs (range: 7.7 to 63.26 g) including traditional IBS addressed both sex and the mean age of patients ranging from
dietary advice, the standard diet based on NICE guidelines, 28 to 55 years. The characteristics of the included meta-ana-
gluten-free diet, sham diet, habitual diet, and high FODMAPs lysis and clinical trial studies are summarized based on the
diet) on clinical outcomes including a clinical improvement in outcomes in Tables S3 and S4.†
IBS-SSS (n = 13 studies used IBS-SSS
tool3,52,53,56,60–63,65,67,69,71,72), total GI symptoms, abdominal 3.2. Methodological quality
pain intensity, abdominal pain frequency, abdominal disten- Among the 11 meta-analyses included in this review, 3 were
sion, dissatisfaction of bowel habit, interference with life in performed by using high-quality methods (AMSTAR score ≥ 8).
general (n = 6 studies used VAS, n = 1 BISS,57 and n = 1 One study was conducted with moderate quality (AMSTAR
GSRS69,71 for symptoms assessment), stool consistency, stool scores 6 and 7), while the remaining 7 studies were of low to
frequency (n = 9 studies used BSF,52,55,56,64,68,69,71–73 and n = critically low quality. As mentioned earlier, the main reasons
1 KSC58), diarrhea, constipation, incomplete defecation, for lower quality scores were due to the fact that the included
urgency of defecation, bloating, flatulence, borborygmus, meta-analyses did not provide appropriate protocols, did not
belching, abdominal discomfort, heartburn, nausea, hydrogen match the registered protocols, did not use a comprehensive
and methane breath tests,62 fecal SCFA,59,73 microbiome in literature search strategy, and did not describe the included
fecal samples,3,51,59,60,68,70,73 lethargy, quality of life (n = 11 studies in adequate details (Table S5†). The study quality and

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risk of bias assessment of primary trials showed the quality of of defecation (Fig. S2c†) compared to the control groups.
studies was good (n = 3), poor (n = 16), and fair (n = 5) Alternatively, a reduction in other symptoms including flatu-
(Table S6†). lence (Hedges: −0.46, 95% CI: −0.67, −0.25) (Fig. S2d†),
incomplete defecation (Hedges: −0.28, 95% CI: −0.51, −0.04)
3.3. Certainty of evidence (Fig. S2e†), borborygmus (WMD: −0.21, 95% CI: −0.26, −0.15)
According to the GRADE tool used to assess certainty of the (Fig. S2f†), and increased heartburn (WMD: 0.08, 95% CI: 0.03,
evidence of eligible meta-analyses for the present umbrella 0.13) (Fig. S2g†) was observed following the diet (Table 1).
review, 24 outcomes revealed that they were rated moderate (n 3.4.2. Effect on stool consistency and frequency. A total of
= 2), low (n = 5), and very low (n = 17). The GRADE scores for 9 RCTs from 5 meta-analysis with 655 to 668 participants
each outcome are demonstrated in detail in Table S7.† showed that an LFD significantly improved stool consistency
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(WMD: −0.48, 95% CI: −0.902, −0.07) and frequency (WMD:

3.4. Findings from the umbrella review and meta-analysis −0.36, 95% CI: −0.61, −0.10) (Fig. S3a and c†). With regard to
3.4.1. Effect on clinical improvement in total and sub- stool consistency, the effect was significant in more than 4
scales of IBS-SSS and other GI symptoms. An overview of the weeks of intervention (Hedges: −0.53, 95% CI: −0.73, −0.32) in
effect of an LFD on GI symptoms is shown in Table 1. As can IBS-D patients (Hedges: −0.84, 95% CI: −1.43, −0.25).
be seen, there was low certainty of evidence for the beneficial Compared to the control group, this significant effect was seen
effect of a low FODMAP diet on the clinical improvement of when patients had a regular diet and did not receive co-inter-
IBS-SSS total score (RR: 1.42, 95% CI: 1.02, 1.97) (Fig. S1a†) vention. Also, stool frequency reduction was seen in IBS-D
specifically in studies with an intervention duration of fewer patients (WMD: −0.61, 95% CI: −1.02, −0.19), but this effect
than 4 weeks (RR: 1.63, 95% CI: 1.28, 2.09). We found that remained in both time durations of less than 4 weeks (WMD:
primary trials with high quality study designs showed the most −0.30, 95% CI: −0.56, −0.04) and more than 4 weeks (WMD:
positive effect (RR: 2.24, 95% CI: 1.40, 3.59). There was moder- −0.69, 95% CI: −1.00, −0.38) of diet intervention. However, a
ate heterogeneity between studies, as shown in Table S8.† significant effect for both stool consistency and frequency was
Moreover, there were 19 trials from 10 meta-analyses with 1214 seen in poor quality evidence, and the high heterogeneity was
participants on total symptoms. They were assessed by observed between the trials (see Table 1 and Tables S16, S17†).
different tools, revealing that an LFD relieved total symptoms The analysis of 4 RCTs for diarrhea and 3 RCTs for consti-
(WMD: −44.97, 95% CI: −65.15, −24.79; and Hedges: −0.56, pation from 3 meta-analyses revealed that LFD versus other
95% CI: −0.70, −0.41) (Fig. 2a and Fig. S1b†) both in short- diets had a significant effect on improving the diarrhea
(Hedges: −0.55, 95% CI: −0.69, −0.40) and long-term (Hedges: (Hedges: −0.45, 95% CI: −0.70, −0.21) (Fig. S3d†) and consti-
−0.58, 95% CI: −0.97, −0.19) period in all subtypes of IBS and pation (WMD: −0.10, 95% CI: −0.14, −0.06) (Fig. S3e†) of IBS
in any study design and quality. Also, compared to any type of patients (Table 1).
diet intervention in the control group, an LFD was shown to 3.4.3. Effects on quality of life. A total of 11 RCTs from
have a significant effect on total symptoms, specifically diets 4 meta-analyses with 1047 participants showed a significant
without co-interventions. There was low heterogeneity between positive effect of an LFD on the quality of life (WMD: 3.53,
studies, as shown in Table S9.† 95% CI: 0.50, 6.55) (Fig. S4a†) in studies assessing all subtypes
In particular, an improvement in every subscale of IBS-SSS of IBS (WMD: 6.38, 95% CI: 2.99, 9.77) with moderate hetero-
including the abdominal pain intensity (Hedges: −0.32, 95% geneity. However, a significant effect was seen in poor-quality
CI: −051, −0.13) (Fig. 2b), abdominal pain frequency (Hedges: studies (WMD: 4.75, 95% CI: 0.13, 9.36). In the comparison
−0.27, 95% CI: −0.45, −0.08) (Fig. 2c and Fig. S1c†), abdomi- between groups, this significant effect was seen when patients
nal distension (WMD: −11.63, 95% CI: −15.89, −7.37) in the control group were on a regular diet and did not receive
(Fig. 2d), dissatisfaction of bowel habit (Hedges: −0.46, 95% co-intervention with diet (see Table S18†).
CI: −0.62, −0.30) (Fig. 2e), and interference on life in general 3.4.4. Effects on anxiety and depression. The meta-analysis
(WMD: −10.70, 95% CI: −19.78, −1.61) (Fig. 2f ) was observed. of 5 trials with 377 participants showed that an LFD interven-
This effect remained significant in less and more than 4 tion versus other diets did not have a significant effect on
weeks. The implementation of the diet for more than 4 weeks anxiety (Fig. S4b†) and depression (Fig. S4c†). There was mod-
did not have a significant effect on the quality of life in erate heterogeneity between studies. However, the feeling of
general. A significant effect was observed in the control group lethargy was significantly reduced (WMD: −0.12, 95% CI:
when participants followed a regular or high FODMAP diet −0.18, −0.07) (Fig. S4d†) (Table 1).
and did not have co-interventions (see Tables S10–S14†).
Analysis of 8 trials from 4 meta-analyses with 687 partici- 3.5. Findings from the systematic review
pants revealed that an LFD could not affect bloating (Hedges: 3.5.1. Fecal microbial diversity and bacterial profiles. A
−0.03, 95% CI: −0.31, 0.24) (Fig. S2a†). However, high hetero- total of 8 trials51,59,68–71,73,74 assessed the global microbiome
geneity was detected between studies, which can be related to composition. A fecal microbiota dysbiosis index (DI) and bac-
the type of study design or tools of symptom assessment terial profile revealed an increase in DI scores in 42% of
(Table S15†). Also, after the implementation of the diet, there patients following the LFD, while a reduction in DI scores was
was no significant change in belching (Fig. S2b†) and urgency seen in 33% of patients on traditional IBS dietary advice51 and

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Table 1 Main analysis on the effects of a low FODMAP diet vs. other diets on the different outcomes in IBS patients

Number Number of P-Value for publication

Review

Outcome of trials participants WMD/Hedges’ g (CI 95%) P-Effectb Q statistic P-Heterogeneity I2 (%) bias (Egger’s test)

Total symptom Hedges’ g 19 1214 −0.56 (−0.70, −0.41) <0.001 29.01 0.05 38 —
WMD 13 854 −44.97 (−65.15, −24.79) <0.001 80.13 <0.001 85 <0.001
Abdominal pain intensity Hedges’ g 19 1257 −0.32 (−051, 0.53) 0.001 51.53 <0.001 65.1 0.631
WMD — — — — — — — —
Abdominal pain frequency Hedges’ g 11 785 −0.27 (−0.45, −0.08) 0.005 18.75 0.04 46.7 —
WMD 11 785 −8.39 (−14.02, −2.77) 0.003 18.29 0.05 45.3 0.531
Abdominal distension Hedges’ g — — — — — — — —
WMD 11 785 −11.63 (−15.89, −7.37) <0.001 12.42 0.26 19.5 0.803
Dissatisfaction of bowel habit Hedges’ g 11 709 −0.46 (−0.62, −0.30) <0.001 12.49 0.25 19.9 0.931
WMD — — — — — — — —

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Interference on life in general Hedges’ g — — — — — — — —
WMD 9 676 −10.70 (−19.78, −1.61) 0.02 87.02 <0.001 90.8 —
Urgency of defecation Hedges’ g 6 444 −0.55 (−1.15, 0.05) 0.075 47.13 <0.001 89.4 —
WMD — — — — — — — —
Bloating Hedges’ g 8 687 −0.03 (−0.31, 0.24) 0.82 28.51 <0.001 75.4 —
WMD — — — — — — — —
Stool frequency Hedges’ g — — — — — — — —
WMD 9 668 −0.36 (−0.61, −0.10) 0.006 25.12 0.001 68.2 —
Stool consistency Hedges’ g 9 655 −0.48 (−0.84, −0.09) 0.02 54.93 <0.001 85.4 —
WMD 8 606 −0.48 (−0.902, −0.07) 0.023 53.70 <0.001 87 —
Diarrhea Hedges’ g 4 260 −0.45 (−0.70, −0.21) <0.001 5.35 0.148 43.9 —
WMD — — — — — — — —
Constipation Hedges’ g — — — — — — — —
WMD 3 190 −0.10 (−0.14, −0.06) <0.001 0.0 1 0.0 —
IBS-QoL Hedges’ g — — — — — — — —
WMD 11 1047 3.53 (0.50, 6.55) 0.02 18.58 0.04 46.2 0.109
HADs-anxiety Hedges’ g — — — — — — — —
WMD 5 377 −0.58 (−1.38, 0.23) 0.159 8.63 0.071 53.6 —
HADs-depression Hedges’ g — — — — — — — —
WMD 5 377 −0.56 (−1.28, 0.15) 0.122 10.51 0.033 61.9 —
Flatulence Hedges’ g 5 347 −0.46 (−0.67, −0.25) <0.001 7.2 0.126 44.5 —
WMD — — — — — — — —
Lethargy Hedges’ g — — — — — — — —
WMD 3 190 −0.12 (−0.18, −0.07) <0.001 6.69 0.035 70.1 —
Incomplete defecation Hedges’ g 4 298 −0.28 (−0.51, −0.04) 0.020 33.63 <0.001 91.1 —
WMD — — — — — — — —
Borborygmus Hedges’ g — — — — — — — —
WMD 3 190 −0.21 (−0.26, −0.15) <0.001 1 0.607 0.0 —
Belching Hedges’ g 3 211 −0.10 (−0.37, 0.17) 0.469 0.19 0.908 0.0 —
WMD — — — — — — — —
Heartburn Hedges’ g — — — — — — — —
WMD 3 190 0.08 (0.03, 0.13) 0.004 2.72 0.257 26.5 —

Outcome Number of trials Number of participants RRa (CI 95%) P-effect Q statistic P-Heterogeneity I2 (%)

Clinical improvement in IBS-SSS 13 804 1.42 (1.02, 1.97) 0.04 35.38 <0.001 66.1 0.940
a
FODMAP: fermentable oligosaccharides, disaccharides, monosaccharides, and polyols; QoL: quality of life; IBS: irritable bowel syndrome; and WMD: weighted mean difference. Reported in
relative risk (RR) and confidence interval (CI) 95%. b P-Value < 0.05 considered significant.
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Fig. 2 Forest plot of randomized controlled clinical trials illustrating weighted mean difference in (a) “total symptoms (WMD)”, (b) “abdominal pain
intensity”, (c) “abdominal pain frequency (WMD)”, (d) “abdominal distention”, (e) “dissatisfaction of bowel habits”, and (f ) “interference in life in
general” between the low FODMAP diet and control groups for all eligible studies in overall analysis. Analysis was conducted using the random
effects model.

sham diet.69 The α-diversity and β-diversity were not different capable of impairing the mucosal barrier)59,68,71,73 in IBS
before and after high or low FODMAP diets among samples patients with moderate to severe symptoms severity, which can
across all types of IBS.68 Alternatively, the LFD reduced total be connected to lactose consumption,59 although β-galacto-
bacterial abundance compared to the habitual diet.59 More oligosaccharides were added to the diet as a prebiotic.71 Also,
precisely, LFD was associated with reduced Bifidobacterium, the microbial diversity in the Clostridium cluster XIV was
Actinobacteria, and Fusobacterium ( proinflammatory bacterium greater in patients on an LFD and the abundance of

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A. muciniphila was greater in those on the control diet59 but no trials published between 2012 and 2022, suggest that an LFD
alteration in bacterial profile was seen with the traditional IBS has beneficial effects on the IBS-SSS total score, subscales of
dietary advice.51 Similarly, LFD was compared with the sham IBS-SSS (abdominal pain frequency, abdominal distension,
diet, higher Bacteroides, and lower Bifidobacterium.69,70 dissatisfaction of bowel habit, and interference with life in
Changes in DI did not differ among responders and non- general), total symptoms, flatulence, incomplete defecation,
responders.74 Therefore, probiotic supplementation to buffer borborygmus, heartburn, quality of life, stool consistency and
the impact of an LFD on Bifidobacterium is recommended.70 frequency, feeling lethargic, diarrhea, and constipation.
3.5.2. Fecal SCFAs. An LFD was associated with higher However, the implementation of an LFD, according to our
fecal pH and lower or similar SCFA in the control groups who findings, has no significant effect on abdominal pain inten-
received a regular diet.59,71,73,75 The fecal butyrate concen- sity, belching and urgency of defecation, anxiety and
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trations decreased, whereas i-butyric and i-valeric acids depression, and bloating in patients with IBS. According to the
increased in the LFD group compared to the control subgroup analysis, the significant positive effects of an LFD on
group.59,71 Thus, a long-term diet restriction should not be IBS-SSS total score were observed when the duration of inter-
advised.71 However, a study showed there was no difference in vention was less than 4 weeks. In addition, the beneficial
total or individual fecal SCFA and pH between groups.68 effects of an LFD on stool consistency were observed if the dur-
3.5.3. Breath test. Three trials reported lactose and ation of intervention was more than 4 weeks. We found moder-
methane breath tests.58,62,64 The hypotheses are based on the ate-quality evidence for the effects of an LFD on abdominal
belief of the potential usefulness of breath tests to identify pain intensity and IBS-QOL. We found low-quality evidence for
patients who will benefit from a reduction in FODMAPs. A sig- IBS-SSS, total symptoms (Hedges as effect size), abdominal
nificant decrease in post-prandial hydrogen H2 production was pain frequency, dissatisfaction of bowel habit and abdominal
seen in the lactulose breath test (LBT) after the implemen- distension. For other outcomes, the quality of the evidence
tation of an LFD compared to the high FODMAP group or brief was very low.
advice on a commonly recommended diet (BRD). However, After subgroup analysis based on the study design, study
there were no significant differences in the methane measure- duration, control diet, co-intervention with diet, population,
ments between the groups. Moreover, significant correlations diagnosis method, and study quality, we found that except for
were observed between bacterial abundance and symptoms, the population and study quality in subgroup analysis of the
and H2 production.62,64 RCTs on the effect of a low FODMAP diet on “stool frequency”,
3.5.4. Nausea. Data from 4 trials66,68,69,71 revealed the sig- other variables were not a source of heterogeneity. The popu-
nificant effect of an LFD on nausea in the 4–6 weeks and lation and study quality can be sources of heterogeneity in the
6 months compared to general dietary advice and regular analysis because they represent potential differences in the
diet;66,71 however, another study did not detect a significant characteristics of the participants and the rigor of the study
effect within the group from the baseline and between groups design. Differences in the populations studied, such as under-
after intervention in 4 weeks.68,69 lying health conditions, can introduce variability that may
impact the results. Similarly, variations in study quality, such
3.6. Publication bias as the use of different assessment tools or methodologies, can
Publication bias was estimated for the outcomes evaluated in lead to differences in the reported outcomes. Alternatively,
more than 10 trials including total symptoms, clinical variables such as study duration, control diet, co-intervention
improvement in IBS-SSS, abdominal pain frequency and inten- with diet, and diagnosis method, may not necessarily contrib-
sity, dissatisfaction of bowel habit, abdominal distention, and ute to heterogeneity if they are consistent across studies or if
IBS-QoL. The funnel plot was asymmetric (Fig. S5†), and a sig- their impact is accounted for in the analysis.
nificant publication bias was detected for trials reporting total The probable mechanisms of the beneficial effects of an
symptoms (P < 0.001 for Egger’s test). The trim-and-fill LFD on IBS and its related complications were studied in
method was used to adjust the results for the potential effect numerous prior clinical investigations. It is believed that an
of publication bias, and after the imputing missing studies, LFD functions by reducing the absorption of osmotically active
the random effect model showed no significant effect in total short-chain carbohydrates in the small intestine, resulting in a
symptoms following the LFD diet (WMD: −14.107; 95% CI: diminished intestinal water content and downstream effects
−34.71, 6.50). There was no significant publication bias for on colonic fermentation and gas production.76,77 Studies have
other clinical outcomes. shown that FODMAP diets increase the fermentable load and
proximal colon liquid delivery in ileo-stomates.78 A high
FODMAP diet increases breath hydrogen across the day due to
4. Discussion fermentative mechanisms occurring in the large intestine, as
shown by the breath hydrogen analysis of individuals with IBS
Although emerging evidence verifies the beneficial effects of and healthy controls.79 Consequently, following an LFD
an LFD on IBS, to date, there is no comprehensive umbrella reduces the fermentable load in the colon and reduces gas pro-
review in this regard to the best of our knowledge. The find- duction, thereby relieving IBS symptoms. The effects of an
ings of the present review, summarizing the results of primary LFD on the reduction in the serum interleukins (ILs) IL-6 and

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IL-8, fecal bacteria levels (Actinobacteria, Bifidobacterium, and the secondary efficacy outcome show that the results obtained
Faecalibacterium prausnitzii), fecal total short-chain fatty acids from these studies should be interpreted with caution.
(SCFAs), and n-butyric acid compared to the baseline have also FODMAPs are a large class of small nondigestible carbo-
been reported.75,80–82 hydrates, containing only 1–10 sugars, which are poorly
Despite all the positive effects that following an LFD has on absorbed in the small bowel. Many foods contain FODMAPs,
IBS-related complications and symptoms, numerous studies including fruits and vegetables, legumes, cereals, honey, milk,
have also mentioned some adverse effects. It is common for and other dairy products, and sweeteners.90 In some previous
any restrictive diet to have nutritional concerns; however, there meta-analyses, RCT studies were included without complete
are three concerns that are particularly pertinent to the use of restrictions on FODMAP items,91–96 which can influence the
an LFD diet by patients with IBS. Firstly, instead of using a results. Also, some trials included in previous meta-analyses
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positive diagnostic approach, such as the Rome criteria, an lacked a control group.97–99 In the current study, we tried to
LFD is inappropriately used as a diagnostic test for IBS ( per- provide more accurate results by excluding these studies.
sonal observations) by some health professionals.83 Secondly, Despite the strongpoints of the current review, including
fructans and galacto-oligosaccharides act as prebiotics; thus, running robust statistical analysis, given that it is the first
their restriction may lead to a state of imbalanced gut micro- attempt to compile evidence from published meta-analyses of
flora and a reduction in beneficial bacteria as a consequence RCTs regarding an LFD and IBS-related outcomes, adopting a
of an LFD.59,84 Additionally, the strict reduction of FODMAP systematic and comprehensive search for relevant information,
intake decreases the absolute and relative numbers of strongly inserting missed trials, excluding incorrect trials and a vali-
butyrate-producing bacteria, while increasing mucus-degrad- dated AMSTAR 2 tool to assess the methodological quality of
ing bacteria.59 Alternatively, Harvie et al.85 showed that partici- published meta-analyses, there are some limitations that
pants who adopted an LFD did not see any changes in their should be addressed. Firstly, the number of included trials is
intestinal microbiome. This shows the importance of the rein- low for some outcomes: the number of trials is 3 for constipation,
troduction phase of the diet, which has not been addressed in 4 for diarrhea and 5 for anxiety and depression. Secondly, the
most studies. Finally, the risk of disordered eating behaviors difference among the control groups in the primary studies and
may be increased for people undergoing dietary changes and employment of a non-valid and various questioner for some out-
having gastrointestinal disorders.86 comes (total symptoms) have led to an increase in the heterogen-
Consistent with our findings about the effects of an LFD on eity, reducing the possibility of comparison. Thirdly, in most of
IBS, the meta-analysis by Hahn et al.87 including 22 studies the primary studies, only the FODMAP limitations have been
revealed that a low FODMAP diet can have positive effects on addressed, while there is a need to conduct studies with a longer
total symptoms, abdominal pain intensity, abdominal pain fre- intervention period, where the reintroduction and personalization
quency, abdominal distension, dissatisfaction of bowel habit, phases are considered. Fourthly, the study of Hahn et al.,87 which
stool consistency, and IBS-QoL. However, this study had some is considered the main meta-analysis for most outcomes,
limitations including the lack of standardization among reported the effect size by SMD. Fifthly, we did not find high-
studies, FODMAP diet varying across different geographical quality evidence for the effect of an LFD on IBS-related outcomes.
regions, and some outcome assessments conducted by using a Additionally, 92% of outcomes had low or very low quality of evi-
poor or not well-explained methodology. Our findings indicate dence. Consequently, more research is needed for outcomes with
that an LFD has beneficial effects on stool frequency (WMD: low or very low certainty of evidence. Sixthly, we selected and
−0.36, 95% CI: −0.61, −0.10) and IBS-SSS total score (RR: 1.42, included published meta-analyses with the largest number of
95% CI: 1.02, 1.97). A meta-analysis performed in 2021,88 primary RCTs and with similar outcomes. However, almost all
revealing that an LFD may be effective in the reduction of the the included meta-analyses stated that they searched the refer-
total IBS-SSS score [n = 354; MD = −37.72], reduction trend of ence lists of all relevant meta-analyses, and therefore it is unlikely
stool frequency [n = 434; MD = −0.28], and improvement in that some primary studies have been missed due to the inclusion
stool consistency [n = 434; (MD) = −0.25]. The results obtained of meta-analyses with the largest number of primary studies.
from this study can be affected by the low sample size of the Finally, in most included primary studies, a classification based
included studies, not using a unified evaluation scale, such as on the type and severity of IBS was not done.
IBS-SSS, to evaluate the overall symptoms of IBS, and the lack
of a classification based on the type of IBS. According to the
network meta-analysis,39 compared with five alternative inter- 5. Conclusion
ventions for IBS, an LFD ranked first in all analyses.
Furthermore, Jung Yu et al.,89 in a network study, revealed that Our umbrella review suggests that low FODMAP diets are ben-
starch- and sucrose-reduced, low FODMAP, and gluten-free eficial for some outcomes, including GI symptoms such as
diets had superior effects on reducing IBS symptoms. Some abdominal pain, abdominal distension and discomfort, stool
limitations such as trials with a high risk of bias, challenges of consistency and frequency in the short and long term; thereby,
choosing an appropriate control group, lack of a unified stan- improving the quality of life. However, a few studies reported
dard definition as a criterion for the inclusion of patients in that an LFD can lead to dysbiosis (reduce Bifidobacterium) and
different studies, and the high heterogeneity in the analysis of increase fecal pH via a reduction in SCFA production.

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According to small pooled effect sizes, and low or very low cer- analysis and had primary responsibility for the final content;
tainty of the evidence in primary trials, further RCTs are M. K. S., S. M. G., Z. E., and S. S. wrote the original draft; S. S.,
needed to reach more reliable conclusions. In addition, more F. S., and A. D. contributed to reviewing and revising the
research with a longer follow-up duration, addressing reintro- paper. A. D. made the revisions related to the English language
duction and personalization phases, is needed to assess the of the text. All authors read and approved the final
long-term effects. manuscript.

Abbreviations Conflicts of interest

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AMSTAR A measurement tool to assess systematic reviews The authors declared that there were no conflicts of interest.
BRD Brief recommended diet
BISS Birmingham IBS symptom score
BSF Bristol stool form Acknowledgements
CI Confidence interval This research did not receive any specific grant from funding
FODMAP Fermentable oligosaccharides, disaccharides, agencies in the public, commercial, or not-for-profit sectors.
monosaccharides and polyols We thank the research team for their cooperation and also the
GRADE Grading of recommendations assessment devel- professional English language editing of this paper by a faculty
opment, and evaluation member of English language Department of Iran University of
GI Gastrointestinal Medical Sciences. We are grateful for the support of Iran
GSRS Gastrointestinal symptom rating scale University of Medical Sciences for conducting this study.
HADs Hospital anxiety and depression scale
KSC King’s stool chart
LFD Low FODMAP diet References
NM Not mentioned
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